The transcription factor Myc drives metabolic reprogramming of activated T cells downstream of mTOR.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Mouse |
| Journal | Immunity |
| Year | 2011 |
| Peer reviewed | Yes |
| Source | DOI 10.1016/j.immuni.2011.09.021 · PMID 22195744 · Free full text (PMC3248798) |
To fulfill the bioenergetic and biosynthetic demand of proliferation, T cells reprogram their metabolic pathways from fatty acid beta-oxidation and pyruvate oxidation via the TCA cycle to the glycolytic, pentose-phosphate, and glutaminolytic pathways. Two of the top-ranked candidate transcription factors potentially responsible for the activation-induced T cell metabolic transcriptome, HIF1alpha and Myc, were induced upon T cell activation, but only the acute deletion of Myc markedly inhibited activation-induced glycolysis and glutaminolysis in T cells. Glutamine deprivation compromised activation-induced T cell growth and proliferation, and this was partially replaced by nucleotides and polyamines, implicating glutamine as an important source for biosynthetic precursors in active T cells. Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines. Therefore, a Myc-dependent global metabolic transcriptome drives metabolic reprogramming in activated, primary T lymphocytes. This may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.
| Intervention | Genetic (Myc) |
| Target | Myc (mTOR-linked metabolism) |
| Model | Mouse T cells |
| Effect | Myc controls the metabolic reprogramming (glycolysis, glutaminolysis) upon T-lymphocyte activation |